One of the principal complications in patients in the intensive care unit, particularly in those receiving mechanical ventilation, is medication-induced delirium. The present study aimed to intensively analyze pharmaceutical factors affecting the development of delirium in mechanically ventilated patients using the electronic health records. The present study was designed as a retrospective case–control study. The delirium group included 500 mechanically ventilated patients. The non-delirium group included 2,000 patients who were hospitalized during the same period as the delirium group and received mechanical ventilation. A total of seven types of medications (narcotic analgesics, non-narcotic analgesics, psychopharmaceuticals, sleep aid medications, anticholinergics, steroids, and diuretics), conventionally used to manage mechanical ventilation, were found to be major risk factors associated with the occurrence of delirium. Since these medications are an integral part of managing mechanically ventilated patients, prudent protocol-based medication approaches are essential to decrease the risk of delirium.
AksuR.AkinA.BicerC.EsmaogluA.TosunZ.BoyaciA. (2009). Comparison of the effects of dexmedetomidine versus fentanyl on airway reflexes and hemodynamic responses to tracheal extubation during rhinoplasty: A double-blind, randomized, controlled study. Current Therapeutic Research, 70(3), 209-220. doi:10.1016/j.curtheres.2009.06.003
2.
Al SutariM. M.AbdalrahimM. S.Hamdan-MansourA. M.AyasrahS. M. (2014). Pain among mechanically ventilated patients in critical care units. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences, 19(8), 726-732.
3.
BalasM. C.VasilevskisE. E.BurkeW. J.BoehmL.PunB. T.OlsenK. M.. . . ElyE. W. (2012). Critical care nurses’ role in implementing the “ABCDE bundle” into practice. Crit Care Nurse, 32(2), 35-38, 40-37; quiz 48. doi:10.4037/ccn2012229
4.
BarbateskovicM.LarsenL. K.Oxenboll-ColletM.JakobsenJ. C.PernerA.WetterslevJ. (2016). Pharmacological interventions for delirium in intensive care patients: A protocol for an overview of reviews. Systematic Reviews, 5(1), 211. doi:10.1186/s13643-016-0391-5
5.
BaronR.BinderA.BiniekR.BrauneS.BuerkleH.DallP.. . . WeisshaarG. (2015). Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015)—short version. GMS German Medical Science, 13, Doc19. doi:10.3205/000223
6.
BarrJ.FraserG. L.PuntilloK.ElyE. W.GelinasC.DastaJ. F.. . . JaeschkeR. (2013). Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Critical Care Medicine, 41(1), 263-306. doi:10.1097/CCM.0b013e3182783b72
7.
BaumgartenM.PoulsenI. (2015). Patients’ experiences of being mechanically ventilated in an ICU: A qualitative metasynthesis. Scandinavian Journal of Caring Sciences, 29(2), 205-214. doi:10.1111/scs.12177
8.
BouadmaL.WolffM.LucetJ. C. (2012). Ventilator-associated pneumonia and its prevention. Current Opinion in Infectious Diseases, 25(4), 395-404. doi:10.1097/QCO.0b013e328355a835
9.
BulicD.BennettM.RodgersH.NourseM.RubieP.LooiJ. C.Van HarenF. (2017). Delirium after mechanical ventilation in intensive care units: The cognitive and psychosocial assessment (CAPA) study protocol. JMIR Research Protocols, 6(2), e31. doi:10.2196/resprot.6660
10.
CampbellM. L. (2015). Caring for dying patients in the intensive care unit: Managing pain, dyspnea, anxiety, delirium, and death rattle. American Association of Critical-Care Nurses Advanced Critical Care, 26(2), 110-120; quiz 121-112. doi:10.1097/nci.0000000000000077
11.
CleggA.SiddiqiN.HeavenA.YoungJ.HoltR. (2014). Interventions for preventing delirium in older people in institutional long-term care. The Cochrane Database of Systematic Reviews, 1, CD009537. doi:10.1002/14651858.CD009537.pub2
12.
CleggA.YoungJ. B. (2011). Which medications to avoid in people at risk of delirium: A systematic review. Age Ageing, 40(1), 23-29. doi:10.1093/ageing/afq140
13.
DaleC. R.KannasD. A.FanV. S.DanielS. L.DeemS.YanezN. D.3rd. . . TreggiariM. M. (2014). Improved analgesia, sedation, and delirium protocol associated with decreased duration of delirium and mechanical ventilation. Annals of the American Thoracic Society, 11(3), 367-374. doi:10.1513/AnnalsATS.201306-210OC
14.
DegradoJ. R.AngerK. E.SzumitaP. M.PierceC. D.MassaroA. F. (2011). Evaluation of a local ICU sedation guideline on goal-directed administration of sedatives and analgesics. Journal of Pain Research, 4, 127-134. doi:10.2147/jpr.s18161
15.
DevR.Del FabbroE.BrueraE. (2011). Patient-controlled analgesia in patients with advanced cancer. Should patients be in control?Journal of Pain and Symptom Management, 42(2), 296-300. doi:10.1016/j.jpainsymman.2010.11.020
16.
ElyE. W.InouyeS. K.BernardG. R.GordonS.FrancisJ.MayL.. . . DittusR. (2001). Delirium in mechanically ventilated patients: Validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA, 286(21), 2703-2710. Retrieved from https://jamanetwork.com/journals/jama/articlepdf/194422/JCE10051.pdf
17.
GillisC. M.PoyantJ. O.DegradoJ. R.YeL.AngerK. E.OwensR. L. (2014). Inpatient pharmacological sleep aid utilization is common at a tertiary medical center. The Society of Hospital Medicine, 9(10), 652-657. doi:10.1002/jhm.2246
18.
HetlandB.LindquistR.ChlanL. L. (2015). The influence of music during mechanical ventilation and weaning from mechanical ventilation: A review. Heart Lung, 44(5), 416-425. doi:10.1016/j.hrtlng.2015.06.010
19.
JeonK.JeongB. H.KoM. G.NamJ.YooH.ChungC. R.SuhG. Y. (2016). Impact of delirium on weaning from mechanical ventilation in medical patients. Respirology, 21(2), 313-320. doi:10.1111/resp.12673
20.
JubranA.LawmG.KellyJ.DuffnerL. A.GungorG.CollinsE. G.. . . TobinM. J. (2010). Depressive disorders during weaning from prolonged mechanical ventilation. Intensive Care Medicine, 36(5), 828-835. doi:10.1007/s00134-010-1842-4
21.
KosarC. M.TabloskiP. A.TravisonT. G.JonesR. N.SchmittE. M.PuelleM. R.. . . InouyeS. K. (2014). Effect of preoperative pain and depressive symptoms on the development of postoperative delirium. Lancet Psychiatry, 1(6), 431-436. doi:10.1016/s2215-0366(14)00006-6
22.
KwizeraA.NakibuukaJ.SsemogerereL.SendikadiwaC.ObuaD.KizitoS.. . . NakasujjaN. (2015). Incidence and risk factors for delirium among mechanically ventilated patients in an African intensive care setting: An observational multicenter study. Critical Care Research and Practice, 2015, 491780. doi:10.1155/2015/491780
23.
LiuK. B.WangD. H.MaY.XiaR. (2013). Remifentanil for analgesia and sedation in mechanically ventilated patients in intensive care unit. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 25(3), 167-170.
24.
MaccariJ. G.TeixeiraC.GazzanaM. B.SaviA.Dexheimer-NetoF. L.KnorstM. M. (2015). Inhalation therapy in mechanical ventilation. Jornal Brasileiro de Pneumologia, 41(5), 467-472. doi:10.1590/s1806-37132015000000035
25.
MaldonadoJ. R. (2008). Pathoetiological model of delirium: A comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment. Critical Care Clinics, 24(4), 789-856, ix. doi:10.1016/j.ccc.2008.06.004
MehtaS.CookD.DevlinJ. W.SkrobikY.MeadeM.FergussonD.. . . BurryL. (2015). Prevalence, risk factors, and outcomes of delirium in mechanically ventilated adults. Critical Care Medicine, 43(3), 557-566. doi:10.1097/ccm.0000000000000727
28.
MichalopoulosA. S.FalagasM. E. (2014). Inhaled antibiotics in mechanically ventilated patients. Minerva Anestesiol, 80(2), 236-244.
29.
MisraU. K.KalitaJ.BetaiS.BhoiS. K. (2015). Outcome of tuberculous meningitis patients requiring mechanical ventilation. Journal of Critical Care, 30(6), 1365-1369. doi:10.1016/j.jcrc.2015.08.017
30.
MoonK. J.JinY.JinT.LeeS. M. (2018). Development and validation of an automated delirium risk assessment system (Auto-DelRAS) implemented in the electronic health record system. International Journal of Nursing Studies, 77, 46-53. doi:10.1016/j.ijnurstu.2017.09.014
31.
NiK.CaryM.ZarkowskiP. (2007). Carisoprodol withdrawal induced delirium: A case study. Neuropsychiatric Disease and Treatment, 3(5), 679-682. Retrieved from https://www.dovepress.com/getfile.php?fileID=1631
32.
PandharipandeP.CottonB. A.ShintaniA.ThompsonJ.PunB. T.MorrisJ. A.Jr.. . . ElyE. W. (2008). Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. The Journal of Trauma, 65(1), 34-41. doi:10.1097/TA.0b013e31814b2c4d
33.
PisaniM. A.MurphyT. E.AraujoK. L.Van NessP. H. (2010). Factors associated with persistent delirium after intensive care unit admission in an older medical patient population. Journal of Critical Care, 25(3), 540.e541-547. doi:10.1016/j.jcrc.2010.02.009
34.
PunB. T.BalasM. C.Barnes-DalyM. A.ThompsonJ. L.AldrichJ. M.BarrJ.. . . ElyE. W. (2019). Caring for critically ill patients with the ABCDEF bundle: Results of the ICU liberation collaborative in over 15,000 adults. Critical Care Medicine, 47(1), 3-14. doi:10.1097/ccm.0000000000003482
35.
RadtkeF. M.FranckM.LorenzM.LuetzA.HeymannA.WerneckeK. D.SpiesC. D. (2010). Remifentanil reduces the incidence of post-operative delirium. The Journal of International Medical Research, 38(4), 1225-1232. doi:10.1177/147323001003800403
36.
Robles BayonA.Gude SampedroF. (2014). Inappropriate treatments for patients with cognitive decline. Neurologia, 29(9), 523-532. doi:10.1016/j.nrl.2012.05.004
37.
SchmidtM.BanzettR. B.RauxM.Morelot-PanziniC.DangersL.SimilowskiT.DemouleA. (2014). Unrecognized suffering in the ICU: Addressing dyspnea in mechanically ventilated patients. Intensive Care Medicine, 40(1), 1-10. doi:10.1007/s00134-013-3117-3
SerafimR. B.DutraM. F.SaddyF.TuraB.de CastroJ. E.VillarinhoL. C.. . . RoccoJ. R. (2012). Delirium in postoperative nonventilated intensive care patients: Risk factors and outcomes. Annals of Intensive Care, 2(1), 51. doi:10.1186/2110-5820-2-51
40.
ShehabiY.RikerR. R.BokeschP. M.WisemandleW.ShintaniA.ElyE. W. (2010). Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients. Critical Care Medicine, 38(12), 2311-2318. doi:10.1097/CCM.0b013e3181f85759
41.
SongW. S.ChoiJ. C.LeeY. S.NaH. Y.ChoiJ. W.KimW. S.ShinM. H. (2008). The risk factors of delirium in elderly patients with hip fracture: A prospective study. Hip and Pelvis, 20(4), 293-298. Retrieved from http://www.riss.kr/link?id=A75593417
42.
SvenningsenH.TonnesenE. (2011). Delirium incidents in three danish intensive care units. Nursing in Critical Care, 16(4), 186-192. doi:10.1111/j.1478-5153.2011.00421.x
43.
TenoJ. M.GozaloP.KhandelwalN.CurtisJ. R.MeltzerD.EngelbergR.MorV. (2016). Association of increasing use of mechanical ventilation among nursing home residents with advanced dementia and intensive care unit beds. JAMA Internal Medicine, 176(12), 1809-1816. doi:10.1001/jamainternmed.2016.5964
TomlinsonE. J.PhillipsN. M.MohebbiM.HutchinsonA. M. (2017). Risk factors for incident delirium in an acute general medical setting: A retrospective case-control study. Journal of Clinical Nursing, 26(5-6), 658-667. doi:10.1111/jocn.13529
46.
TracyM. F.ChlanL. (2011). Nonpharmacological interventions to manage common symptoms in patients receiving mechanical ventilation. Critical Care Nurse, 31(3), 19-28. doi:10.4037/ccn2011653
47.
TraubeC.SilverG.ReederR. W.DoyleH.HegelE.WolfeH. A.. . . BellM. J. (2017). Delirium in critically ill children: An international point prevalence study. Critical Care Med, 45(4), 584-590. doi:10.1097/ccm.0000000000002250
48.
TsurutaR.OdaY.ShintaniA.NunomiyaS.HashimotoS.NakagawaT.. . . YabeS. (2014). Delirium and coma evaluated in mechanically ventilated patients in the intensive care unit in Japan: A multi-institutional prospective observational study. Journal of Critical Care, 29(3), 472.e471-475. doi:10.1016/j.jcrc.2014.01.021
49.
UmegakiT.SakamotoS.NishiK.OkamotoA.OnoseA.HamanoN.. . . ShinguK. (2014). Impact of steroid medication before hospital admission on barotrauma in mechanically ventilated patients with acute respiratory distress syndrome in intensive care units. Journal of Anesthesia, 28(5), 681-686. doi:10.1007/s00540-014-1799-5
50.
Van RompaeyB.ElseviersM. M.SchuurmansM. J.Shortridge-BaggettL. M.TruijenS.BossaertL. (2009). Risk factors for delirium in intensive care patients: A prospective cohort study. Critical Care, 13(3), R77. doi:10.1186/cc7892
51.
WallaceD. J.AngusD. C.SeymourC. W.BarnatoA. E.KahnJ. M. (2015). Critical care bed growth in the United States. A comparison of regional and national trends. American Journal of Respiratory and Critical Care Medicine, 191(4), 410-416. doi:10.1164/rccm.201409-1746OC
52.
WatneL. O.IdlandA. V.FekkesD.RaederJ.FrihagenF.RanhoffA. H.. . . HasselB. (2016). Increased CSF levels of aromatic amino acids in hip fracture patients with delirium suggests higher monoaminergic activity. BMC Geriatrics, 16, 149. doi:10.1186/s12877-016-0324-0
53.
WeinhouseG. L.SchwabR. J. (2006). Sleep in the critically ill patient. Sleep, 29(5), 707-716.
54.
WongA. K.WalkeyA. J. (2015). Open lung biopsy among critically ill, mechanically ventilated patients. A metaanalysis. Annals of the American Thoracic Society, 12(8), 1226-1230. doi:10.1513/AnnalsATS.201502-077BC
55.
ZhangZ.ChenK.NiH.ZhangX.FanH. (2017). Sedation of mechanically ventilated adults in intensive care unit: A network meta-analysis. Scientific Reports, 7, 44979. doi:10.1038/srep44979
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
